Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Undiagnosed Diseases Network, |
RCV000991217 | SCV001142597 | uncertain significance | EIF2AK2-related disorder | 2019-07-26 | criteria provided, single submitter | clinical testing | Testing for this patient was performed at Ambry. Given the variant is a de novo missense variant, absent in population databases, and unpublished cohort data suggest it is associated with specific neurologic phenotypes, this variant is classified as a variant of uncertain significance. The variant occurred de novo in a patient with neurologic phenotype. The variant is absent in gnomAD. Metrics indicate adequate coverage. As of 9/12/19, there were no published cases of disease causing variants in the EIF2AK2 gene. The EIF2AK2 gene has no established gene-disease association. The gene has a role in the EIF2B pathway, which has been associated with vanishing white matter leukoencephalopathies. However, unpublished laboratory cohort data has identified other unrelated patients with similar neurologic phenotypes to suggest that de novo missense variants are implicated in disease. |
Ambry Genetics | RCV001266299 | SCV001444472 | uncertain significance | Inborn genetic diseases | 2018-11-30 | criteria provided, single submitter | clinical testing | |
SIB Swiss Institute of Bioinformatics | RCV001093623 | SCV001468564 | uncertain significance | Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome | 2020-12-18 | criteria provided, single submitter | curation | This variant is interpreted as a variant of uncertain significance for Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, autosomal dominant The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); de novo variant (PS2 downgraded to moderate); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting). |
OMIM | RCV001093623 | SCV001250815 | pathogenic | Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome | 2022-02-10 | no assertion criteria provided | literature only |